Assessing the Adverse Impacts of PM_(2.5)on Olfactory System Using an Air-liquid Interface Culture Model of Primary Olfactory Epithelial Cells

The air-liquid interface(ALI)culture is a kind of recently developed system,which has proved its availability in simulating the biology of respiratory tract epithelial tissues.In this study,an ALI-based mouse primary olfactory epithelial cell(OEC)model was established to perform the exposure of PM_(2.5)(PM=particulate matter)collected from Dianshan Lake(Shanghai)and Wangdu(Hebei).The results showed that PM_(2.5)in both regions caused a decrease in cell viability in a dose-dependent manner.The 0.5 and 5µg/cm^(2)(around ambient concentrations)of PM_(2.5)disrupted OEC membrane integrity and produced oxidative stress with elevated indicators of malondialdehyde(MDA)and reactive oxygen species(ROS).In transcriptomic sequencing,the terms concerning inflammatory cytokines and second messenger cyclic adenosine-3′,5′-monophoshate(cAMP)were enriched in two treatments.The cytokine array showed the levels of some cytokines were altered,although inflammatory responses may not remarkably occur.Meanwhile,PM_(2.5)disturbed cAMP contents and key genes in the cAMP signaling pathway.The effects of PM_(2.5)of both regions were largely consistent,while Wangdu samples caused more ROS and Dianshan Lake samples tended to induce inflammatory injury.Thus,with the application of a novel ALI-based in vitro OEC model,our study demonstrated that ambient PM_(2.5)has the ability to threaten the physiologies and functions of the olfactory system.

STUDY ON THE MECHANISM OF INTERFERON ACTION (Ⅺ)——EFFECT OF pppA2'p5'A2'p5'A ON THE LEVEL OF cAMP AND cGMP IN MACROPHAGES

In this paper, the increase of cellular cAMP and cGMP levels in macrophages induced bypppA2’p5’A2’p5’A （briefly 2’-5’P3A3） is first reported. The optimal concentration of 2’-5’P3A3 for the elevation of cellular cGMP to the highest level is 10-7-10-6mol/L, while thatfor cAMP is 10-7mol/L. The time for cGMP to reach its peak value is 15 min and that forcAMP is 2 h, when the cells are treated with 2’-5’ P3A3 at 10-7mol/L, which is the optimalconcentration for developing biological effect of macrophages （phagocytosis）. These resultssuggest that cGMP and cAMP may be related to, or may be the mediators for, 2’-5’P3A3action.

Underlying Mechanisms of Memory Deficits Induced by Etomidate Anesthesia in Aged Rat Model： Critical Role of Immediate Early Genes

Background： Etomidate （R- 1 -[ 1 -ethylphenyl] imidazole-5-ethyl ester） is a widely used anesthetic drug that had been reported to contribute to cognitive deficits after general surgery. However, its underlying mechanisms have not been fully elucidated. In this study, we aimed to explore the neurohiological mechanisms of cognitive impairments that caused by etomidate. Methods： A total of 30 Sprague-Dawley rats were used and divided into two groups randomly to receive a single injection ofeiomidate or vehicle. Then, the rats＇ spatial memory ability and neuronal survival were evaluated using the Morris water maze test and Nissl staining, respectively. Furthermore, we analyzed levels of oxidative stress, as well as cyclic adenosine 3＇,5＇-monophosphate response element-binding （CREB） protein phosphorylation and immediate early gene （IEG, including Arc, c-fos, and Egrl） expression levels using Western blot analysis. Results： Compared with vehicle-treated rats, the etomidate-treated rats displayed impaired spatial learning （day 4：27.26 ± 5.33 s vs. 35.52 ± 3.88s, t 2.988, P 0.0068; day 5： 15.84±4.02svs.30.67±4.23s,t=3.013,P=0.0057;day6：9.47±2.35svs.25.66±4.16s,t=3.567, P = 0.0036） and menaory ability （crossing times： 4.40 ± 1.18 vs. 2.06 ± 0.80, t = 2.896, P 0.0072; duration： 34.00± 4.24 s vs. 18.07 ±4.79 s, t = 3.023, P= 0.0053; total swimming distance： 40.73 ±3.45 cm vs. 27.40± 6.56 cm, t = 2.798, P = 0.0086） but no neuronal death. Furthermore, etomidate did not cause oxidative stress or deficits in CREB phosphorylation. The levels of multiple lEGs （Arc： vehicle treated rats 100%, etomidate treated rats 86%, t = 2.876, P 0.0086; c-los： Vehicle treated rats 100%, etomidate treated rats 72%, t =2.996, P = 0.0076; Egrl ： Vehicle treated rats 100%, etomidate treated rats 58%, t = 3.011, P=0.0057） were significantly reduced in hippocampi ofetomidate-treated rats. Conclusion： Our data suggested that etomidate might induce memory impairment in rats via inhibition of lEG expression.